6,7-di-O-acetylsinococuline (FK-3000) induces G2/M phase arrest in breast carcinomas through p38 MAPK phosphorylation and CDC25B dephosphorylation
نویسندگان
چکیده
We evaluated the cytostatic effect of 6,7-di-O-acetyl-sinococuline (FK-3000) isolated from Stephania delavayi Diels. against breast carcinoma cell lines MDA-MB‑231 and MCF-7. FK-3000 suppressed CDC25B phosphorylation directly and indirectly via p38 MAPK phosphorylation. CDC25B dephosphorylation decreased levels of cyclin B and phospho-CDC-2, and ultimately induced cell cycle arrest at the G2/M phase. The p38 MAPK inhibitor, SB 239063 blocked FK-3000-induced p38 MAPK phosphorylation and nuclear accumulation, but did not completely rescue cell death. Conclusively FK-3000 exerts its antiproliferative effect through two pathways: i) G2/M cell cycle arrest via downregulation of cyclin B and phospho-CDC2 by p38 MAPK phosphorylation and CDC25B dephosphorylation, and ii) p38 MAPK-independent induction of apoptosis.
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عنوان ژورنال:
دوره 46 شماره
صفحات -
تاریخ انتشار 2015